Boosting dosages

As a result, if dissolution from formulations is studied exclusively under low pH conditions, the formulators are likely to be in for a rude shock when the results come back from the pharmacokinetic studies—poor and highly variable absorption is the order of the day for drugs that have been formulated without an eye to robustness of the release from the dosage form as a function of pH. Instead, it is recommended that a formulation be sought that can release the drug even when there is not enough acid in the stomach to provide a sufficient boost to the solubility or when the gastric residence time is short. 

In such instances, "boosting may be called for. An additional dosage is usually enough to "break the set and move the user off his or her plateau. Dr. Duncan Blewett gives the rationale ... 

The use of paracetamol as an antipyretic increased rapidly once phenacetin was no longer available and has received a boost more recently with wide acknowledgement of the role of aspirin as a causative agent in Reye s syndrome, resulting in the virtual disappearance of children s dosage forms of aspirin. While the incidence of adverse effects is reassuringly low, satisfaction must be tempered by appreciation of the relatively short duration of extensive clinical experience with paracetamol, its close relation to phenacetin, its low potency as an analgesic, and low public awareness of its potential adverse effects. 

This interaction is of clinical importance be alert for the need to reduce the midazolam dosage in the presence of saquinavir. The authors of the study suggest that continuous intravenous midazolam doses should be reduced by 50%, but do not consider dose adjustments to single intravenous doses necessary. The same precautions would seem appropriate with triazolam. However, the manufacturer of saquinavir contraindicates the concurrent use of oral midazolam and triazolam. They note that no studies have been conducted with ritonavir-boosted saquinavir but that a 3 to 4-fold increase in intravenous midazolam levels would be expected. Use of intravenous midazolam with saquinavir is not contraindicated but they... 

Boelaert JR, Dorn GM, Huitema ADR, Beijnen JH, Lange JMA. The boosting of didanosine by allopurinol permits a halving of the didanosine dosage. AIDS (2002) 16, 2221-3. 

Rifabutin bioavailability is increased by amprenavir, atazanavir, fosamprenavir/ritonavir, indinavir, lopinavir/ritonavir, nelfinavir, tipranavir/ritonavir, and especially ritonavir, with an increased risk of toxicity. Rifabutin modestiy decreases the bioavailability of indinavir, neifinavir, and particuiarly saquinavir (with an increased risk of therapeutic faiiure), but has no effect on amprenavir, atazanavir, and ritonavir-boosted fosamprenavir. The combination of rifabutin with protease inhibitors may be used, but dosage adjustments of rifabutin or both drugs are often necessary. 

Information on this interaction and its clinical relevance is limited. The author of the pharmacokinetic study suggests that, if the drugs need to be used together, the dosage of pentoxifylline should be halved. In the absence of other information, if a short-course of ciprofloxacin is required in a patient taking pentoxifylline, this may be a sensible precaution. Alternatively, because the increase in AUC was minor, it may be sufficient to recommend a reduction in pentoxifylline dose only in those who experience adverse effects (e.g. nausea, headache). Note that ciprofloxacin has been used to boost pentoxifylline levels in studies investigating the possible therapeutic value of pentoxifylline s ability to inhibit various cytokines. For example, ciprofloxacin 500 mg twice daily was used with pentoxifylline 800 mg three times daily for up to one year in patients with myelod-ysplastic syndrome. ... 

Acceleration of CIT kill-rate. To boost the kill rate of isothiazolinones the combination with the O-methylol or N-methylol compounds is an interesting strategy. Of course an increase of the dosage would speed-up the kill... 

Modulation of epidermal lipid biosynthesis has been reported to boost drag delivery. It has also been suggested that it is both the hydrophobic nature of the lipids as well as their tortuous, extracellular localization that are responsible for the restriction in the transport of most molecules across the stratum comeum. The function of this barrier depends on three key lipids cholesterol, fatty acid, or ceramides. Delays of synthesis ceramides in the epidermis have been reported as means of barrier perturbation. Inhibitors of lipid synthesis were used to enhance the trans-A cmaV dehvery of hdocaine or caffeine. Alteration of barrier function was produced by the fatty acid synthesis inhibitor S-(tetradecyloxy)-2-furancarboxylic acid, the cholesterol synthesis inhibitor fluvastatin, or the cholesterol sulfate, which resulted in a further increase in lidocaine absorption (38). The major components of sebaceous lipids in the skin are 45-60% TAGs, 25% wax and sterol esters, 12-15% squalene and 10% free fatty acids (39). Some fatty acids, especially unsaturated fatty acids, are well-known skin penetration enhancers. The addition of PC to dermal dosage forms has been reported to increase percutaneous absorption. Lipid disperse systems (LDSs) containing polar lipids, such as PC and glycosylceramide, are also useful for... 

MEDICINALS Providing over-the-counter medications to ill employees can improve and sustain productivity, help boost morale and performance, and decrease accidents and absenteeism. While the employer may make OTC medications available in unit-dosage, tamper-evident packaging that complies with FDA labeling requirements, the employee requesting them assumes... 

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